Indian Journal of Hematology and Blood Transfusion最新文献

Over recent decades, UCB has been widely used as an excellent alternative source of HSCs for treating many hematologic disorders. Recent studies suggest using mesenchymal stroma cell co-cultures to increase the number of HSCs prior to transplantation. Considering the critical role of mitochondria in the cell's fate and the importance of the self-renewal capacity of HSCs in HSCT, we decided to investigate the mass/DNA copy number of mitochondria in HSCs while co-cultured with MSCs and alone after seven days. UCB units were collected from full-term deliveries. MSCs and HSCs were isolated from UCB and the purity of cells was confirmed by flow cytometry. The mtDNA-Copy Number of HSCs was calculated using prob-based real-time PCR. Furthermore, Mito Tracker Green dye measured the mass of mitochondria of HSCs. HSCs from MSC co-culture group showed significantly fewer mtDNA-CN compared to HSCs alone after seven days (p < 0.001). Besides, by comparing the two groups on day seven to HSCs on day zero, we observed a mild increase in the mitochondrial mass of HSCs alone compared to the MSC-HSC co-culture group (p < 0.05). Concerning previous studies that have proved the association between lower mass/DNA-copy number of mitochondria in CD34 + HSCs and lower metabolic activity along with higher quiescence maintenance, and by considering the results of this experiment, it seems that the MSC-HSC co-cultures might be associated with a higher expansion of HSCs as well as stemness maintenance leading to the improvement in engraftment. Nevertheless, further investigations are required to clarify the exact connection between lower mass/DNA-copy number of mitochondria and stemness maintenance in HSCs.

Revised International Prognostic (R-IPI) score is used widely for risk stratification of DLBCL cases, yet some patients belonging to same risk category tend to exhibit different outcomes. The role of T-cells and macrophages in prognostication of lymphomas has been a point of interest of late. We aimed to study the association of FOXP3 positive T-regulatory cells, cytotoxic T-cells and macrophages with the immunophenotypic subtypes, clinicopathological characteristics, treatment response and survival in nodal diffuse large B-cell lymphoma (DLBCL) patients. The clinicopathological and treatment data of 83 DLBCL patients diagnosed and treated at our institute from January 2015 to December 2018 were collected and followed up till June 2020. CD8, FOXP3 and CD68 immunostains were performed to highlight the cytotoxic T-cells, T-regulatory cells and macrophages respectively on the lymph node biopsies and the distribution of these cells and their association with clinico-pathological factors, treatment response and survival was analyzed. DLBCL cases with higher percentage of CD3 positive T-cells and CD8 positive cytotoxic T-cells had significant association with attainment of complete response to treatment. In addition, CD8 positive T-cells of more than 6.5% proved to be an independent predictor of treatment outcome (p = 0.022). Multivariate Cox regression survival analysis revealed that cases with ‘good’ R-IPI prognostic score and ‘high CD68 positive macrophages in tumor microenvironment’ had a significantly longer overall survival. Increased number of cytotoxic T-cells was significantly associated with complete response to treatment and higher number of macrophages correlated significantly with better overall survival signifying their antitumor effects.

To find the independent factors affecting the prognosis of AITL patients, establish a novel predictive model, and stratify the prognosis of AITL patients. We retrospectively analyzed the clinical data of 86 patients diagnosed with AITL in the First Affiliated Hospital of Wenzhou Medical University from December 2010 to March 2022. The clinical features, recurrence time, and death time of patients were collected and analyzed statistically. The median age of our patients was 68 years old, and the male-to-female ratio was 2.2: 1. There are differences between males and females in ECOG PS score (p = 0.037), β2 microglobulin levels (p = 0.018) and IgM (p = 0.021). Multivariate COX regression analysis showed that C-reactive protein > 39.3 mg/L (hazard ratio (HR), 5.41; p = 0.0001), Age > 66 years (hazard ratio (HR), 3.06; p = 0.0160), Ki67 positive (hazard ratio (HR), 4.86; p = 0.0010) and early progression of disease within 24 months (POD24) after diagnosis (hazard ratio (HR), 12.47; p = 0.0001) were independent factors affecting the prognosis of OS. KM analysis showed that the predictive model established by these four factors could effectively predict the prognosis of patients with AITL (p < 0.0001), and the ROC curve showed that the predictive ability of the new predictive model (AUC = 0.909) was significantly better than that of the traditional predictive models, such as IPI (AUC = 0.730), PIT (AUC = 0.720), PIAI (AUC = 0.715) and AITL score (AUC = 0.724). Age, C-reactive protein, Ki67, and POD24 were independent factors affecting the prognosis of OS. The prognostic model established by them combined clinical features, and serological and pathological indicators and could effectively predict the prognosis of AITL patients.

Developing resistance to anticancer drugs complicates the clinical treatment of multiple myeloma patients. Previous studies revealed a link between the unfolded protein response (UPR) and miRNAs with acquired drug resistance. This study aimed to determine the expression profile of XBP1, hsa-miR-34c-5p, hsa-miR-214, and hsa-miR-30c-2* in resistant and sensitive multiple myeloma cell lines to a proteasome inhibitor, bortezomib. After establishing bortezomib-resistant cells, the expression level of XBP1, hsa-miR-214, hsa-miR-34c-5p, and hsa-miR-30c-2* in both cell lines were assessed by qRT-PCR. Hsa-miR-34c-5p was suppressed to study its effect on the expression profile of Bax/Bcl-2. Statistical analysis was done by t-test in two clinically resistant and sensitive cells to bortezomib. MTT assay confirmed the creation of the resistant cell line. The qRT-PCR screening showed a significant difference between XBP1 and miR-34c-5p levels in resistant and sensitive cells. Following hsa-miR-34c-5p blockage, while Bax was overexpressed, Bcl-2 expression was reduced in the resistant cell line, overcoming cells resistant to bortezomib. Our findings demonstrate miR-34c-5p is differentially expressed between bortezomib-sensitive and -resistant MM cells. Inhibiting miR-34c-5p re-sensitized resistant cells to bortezomib by modulating Bax/Bcl-2 expression, suggesting this miRNA regulates apoptosis and drug resistance and may be a promising therapeutic target for overcoming proteasome inhibitor resistance in MM.

Rearrangement involving ZNF384 gene (ZNF384-r) is recently being described in acute leukemias. We present the clinic-pathological and immunophenotypic findings in a series of five cases of acute leukemia with ZNF384-r reported in our Institute between September 2020 to September 2023. Notably, while TCF3::ZNF384 fusion was the most frequently encountered abnormality, the fusion partner was not identified in two patients with ZNF384-r BCP-ALL. Immunophenotypically, patients presenting as B-cell precursor acute lymphoblastic leukemia (BCP-ALL) had a distinct profile characterized by weak or absent CD10 expression and the presence of myeloid markers such as CD13/CD33. Our findings underscore the importance of recognizing the distinct immunophenotypic features of ZNF384-r leukemias, particularly in cases presenting with atypical BCP-ALL or B/Myeloid mixed phenotype acute leukemia phenotypes. Moreover, these findings highlight the necessity for tailored diagnostic algorithms in clinical laboratories to facilitate the timely and accurate diagnosis of this clinically relevant leukemia subtype.

Abstract

Diagnosing Chronic Myeloid Leukemia (CML) during pregnancy presents challenges for both haematologists and obstetricians. Limited data exists regarding the management of pregnancy-associated CML in low- and middle-income countries (LMICs). This study aimed to assess pregnancy, foetal, and long-term disease outcomes in female patients newly diagnosed with CML in the chronic phase (CML-CP) during pregnancy. A retrospective analysis was conducted on female CML-CP patients presenting between January 2002 and December 2022 at our institution. Inclusion criteria encompassed patients newly diagnosed with CML-CP during pregnancy. Data pertaining to pregnancy outcomes, foetal development, and disease progression were analysed through a comprehensive review of medical records. Among the female CML patients, thirteen were diagnosed with CML-CP during pregnancy. The median patient age was 24 years (range: 20–35). Diagnoses occurred in the first trimester for six patients, the second trimester for three, and the third trimester for four. Outcomes included five elective terminations (38.5%), five pre-term deliveries (38.5%), and three full-term deliveries (23.1%). Management included observation in 6 (46.3%), hydroxyurea in 3 (23.1%), imatinib in 3 (23.1%) and Interferon-α (IFN-α) in 1 (7.7%) patients. Noteworthy obstetric complications encompassed threatened abortion with intrauterine foetal death (IUFD) (1 patient), intrauterine growth retardation (IUGR) (3 patients), oligohydramnios (2 patients), antepartum haemorrhage (1 patient), placental abruption (1 patient), and postpartum haemorrhage (3 patients). At a median follow-up duration of 10.7 years, 11 patients were at a major molecular remission (including 2 patients with deep molecular remission) and two patients progressed to the accelerated phase. The diagnosis and management of CML during pregnancy is a complex and challenging task that requires collaboration between haematologists and obstetricians. Effective management of newly diagnosed CML-CP during pregnancy is contingent on the trimester of presentation. Further research and collaboration are warranted to develop standardised guidelines for managing pregnancy-associated CML, particularly in LMICs.